The Enzyme Database

Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (NC-IUBMB)

Proposed Changes to the Enzyme List

The entries below are proposed additions and amendments to the Enzyme Nomenclature list. They were prepared for the NC-IUBMB by Kristian Axelsen, Ron Caspi, Ture Damhus, Shinya Fushinobu, Julia Hauenstein, Antje Jäde, Ingrid Keseler, Masaaki Kotera, Andrew McDonald, Gerry Moss, Ida Schomburg and Keith Tipton. Comments and suggestions on these draft entries should be sent to Dr Andrew McDonald (Department of Biochemistry, Trinity College Dublin, Dublin 2, Ireland). The date on which an enzyme will be made official is appended after the EC number. To prevent confusion please do not quote new EC numbers until they are incorporated into the main list.

An asterisk before 'EC' indicates that this is an amendment to an existing enzyme rather than a new enzyme entry.


Contents

*EC 1.2.1.82 β-apo-4′-carotenal dehydrogenase
EC 1.3.1.126 2-epi-5-epi-valiolone dehydrogenase
EC 1.6.1.2 transferred
EC 1.8.1.22 dissimilatory sulfite reductase system
EC 1.8.5.10 [DsrC]-trisulfide reductase
EC 1.8.99.5 transferred
*EC 2.1.1.298 ribosomal protein uL3 N5-glutamine methyltransferase
EC 2.1.1.391 demethylgadusol O-methyltransferase
*EC 2.3.1.266 [ribosomal protein bS18]-alanine N-acetyltransferase
*EC 2.3.1.267 [ribosomal protein uS5]-alanine N-acetyltransferase
EC 2.3.3.22 3-carboxymethyl-3-hydroxy-acyl-[acp] synthase
EC 2.4.1.129 transferred
EC 2.4.1.394 4,6-α-glucanotransferase (linear substrates/linear products)
EC 2.4.1.395 reuteransucrase
EC 2.4.1.396 4,6-α-glucanotransferase (linear and branched substrates, branched products)
EC 2.4.99.28 peptidoglycan glycosyltransferase
*EC 2.8.4.4 [ribosomal protein uS12] (aspartate89-C3)-methylthiotransferase
EC 3.1.1.122 carbendazim hydrolysing esterase
*EC 3.1.3.62 multiple inositol-polyphosphate phosphatase
EC 3.1.8.2 transferred
EC 3.2.1.221 MMP endo-(1,4)-3-O-methyl-α-D-mannosidase
EC 3.2.1.222 funoran endo-β-hydrolase
EC 3.2.1.223 arabinogalactan exo α-(1,3)-β-L-arabinopyranosyl-(1→3)-L-arabinofuranosidase (non-reducing end)
EC 3.4.21.123 kumamolysin
*EC 3.4.24.84 Ste24 endopeptidase
EC 3.4 Acting on peptide bonds (peptidases)
EC 3.4.26 Glutamic endopeptidases
EC 3.4.26.1 intramembrane prenyl-peptidase Rce1
EC 3.4.26.2 scytalidoglutamic peptidase
*EC 3.5.1.12 biotinidase
EC 3.8.2.2 diisopropyl-fluorophosphatase
*EC 4.1.1.87 malonyl-[malonate decarboxylase] decarboxylase
EC 4.1.1.124 malonyl-[acp] decarboxylase
EC 4.1.1.125 4-carboxy-3-alkylbut-2-enoyl-[acp] decarboxylase
EC 4.1.1.126 anhydromevalonate phosphate decarboxylase
EC 4.2.1.181 3-carboxymethyl-3-hydroxy-acyl-[acp] dehydratase
EC 4.2.1.182 phosphomevalonate dehydratase
EC 4.2.2.29 peptidoglycan lytic transglycosylase
EC 4.2.3.212 (+)-δ-cadinol synthase
EC 4.2.3.213 colleterpenol synthase
EC 4.2.3.214 dolasta-1(15),8-diene synthase
EC 4.2.3.215 δ-araneosene synthase
EC 4.2.3.216 somaliensene A synthase
EC 4.2.3.217 somaliensene B synthase
EC 4.2.3.218 variediene synthase
EC 4.2.3.219 (2E)-α-cericerene synthase
EC 6.7.1.2 3-aminoavenalumate diazotase
*EC 7.1.1.3 ubiquinol oxidase (H+-transporting)


*EC 1.2.1.82
Accepted name: β-apo-4′-carotenal dehydrogenase
Reaction: 4′-apo-β,ψ-caroten-4′-al + NAD+ + H2O = neurosporaxanthin + NADH + 2 H+
For diagram of reaction, click here
Glossary: neurosporaxanthin = 4′-apo-β,ψ-caroten-4′-oic acid
Other name(s): β-apo-4′-carotenal oxygenase; YLO-1; carD (gene name)
Systematic name: 4′-apo-β,ψ-carotenal:NAD+ oxidoreductase
Comments: Neurosporaxanthin is responsible for the orange color of of Neurospora.
Links to other databases: BRENDA, EXPASY, KEGG
References:
1.  Estrada, A.F., Youssar, L., Scherzinger, D., Al-Babili, S. and Avalos, J. The ylo-1 gene encodes an aldehyde dehydrogenase responsible for the last reaction in the Neurospora carotenoid pathway. Mol. Microbiol. 69 (2008) 1207–1220. [DOI] [PMID: 18627463]
2.  Diaz-Sanchez, V., Estrada, A.F., Trautmann, D., Al-Babili, S. and Avalos, J. The gene carD encodes the aldehyde dehydrogenase responsible for neurosporaxanthin biosynthesis in Fusarium fujikuroi. FEBS J. 278 (2011) 3164–3176. [DOI] [PMID: 21749649]
[EC 1.2.1.82 created 2011, modified 2023]
 
 
EC 1.3.1.126
Accepted name: 2-epi-5-epi-valiolone dehydrogenase
Reaction: 2-epi-5-epi-valiolone + NAD+ = demethylgadusol + NADH + H+
Glossary: 2-epi-5-epi-valiolone = (2S,3S,4S,5R)-2,3,4,5-tetrahydroxy-5-(hydroxymethyl)cyclohexan-1-one
demethylgadusol = (4R,5R)-2,3,4,5-tetrahydroxy-5-(hydroxymethyl)cyclohex-2-en-1-one
Other name(s): gadusol synthase
Systematic name: 2-epi-5-epi-valiolone:NAD+ 2,3-oxidoreductase
Comments: The enzyme, present in egg-laying vertebrates, is involved in biosynthesis of the UV absorbing compound gadusol. It is a bifunctional enzyme that also catalyses EC 2.1.1.391, demethylgadusol O-methyltransferase.
Links to other databases: BRENDA, EXPASY, KEGG
References:
1.  Osborn, A.R., Almabruk, K.H., Holzwarth, G., Asamizu, S., LaDu, J., Kean, K.M., Karplus, P.A., Tanguay, R.L., Bakalinsky, A.T. and Mahmud, T. De novo synthesis of a sunscreen compound in vertebrates. Elife 4 (2015) . [DOI] [PMID: 25965179]
[EC 1.3.1.126 created 2023]
 
 
EC 1.6.1.2
Transferred entry: NAD(P)+ transhydrogenase (Re/Si-specific). Now classified as EC 7.1.1.1, proton-translocating NAD(P)+ transhydrogenase
[EC 1.6.1.2 created 1986, modified 2013, deleted 2023]
 
 
EC 1.8.1.22
Accepted name: dissimilatory sulfite reductase system
Reaction: a [DsrC protein]-trisulfide + NAD+ + 3 H2O = a [DsrC protein]-dithiol + sulfite + NADH + H+
Other name(s): siroheme sulfite reductase; DsrABL; hydrogen-sulfide:(acceptor) oxidoreductase (incorrect)
Systematic name: [DsrC protein]-trisulfide,NAD+ oxidoreductase (sulfite-forming)
Comments: Contains siroheme. The enzyme is essential in prokaryotic sulfur-based energy metabolism, including sulfate/sulfite reducing organisms, sulfur-oxidizing bacteria, and organosulfonate reducers. The system comprises the DsrAB reductase and the DsrL protein, which form a tight complex. The reaction involves the small protein DsrC, which is present in all the organisms that contain dissimilatory sulfite reductase. In sulfite reducers the DsrL component transfers two electrons from NADH to the DsrAB component, which then reduces the sulfur in sulfite to an S(II) intermediate that forms (together with two cysteine residues of DsrC) a trisulfide. In sulfur oxidizers the enzyme catalyses the opposite reaction [1].
Links to other databases: BRENDA, EXPASY, KEGG
References:
1.  Schedel, M., Vanselow, M. and Trueper, H. G. Siroheme sulfite reductase from Chromatium vinosum. Purification and investigation of some of its molecular and catalytic properties. Arch. Microbiol. 121 (1979) 29–36. [DOI]
2.  Seki, Y., Sogawa, N. and Ishimoto, M. Siroheme as an active catalyst in sulfite reduction. J. Biochem. 90 (1981) 1487–1492. [DOI] [PMID: 7338517]
3.  Pott, A.S. and Dahl, C. Sirohaem sulfite reductase and other proteins encoded by genes at the dsr locus of Chromatium vinosum are involved in the oxidation of intracellular sulfur. Microbiology (Reading) 144 (1998) 1881–1894. [DOI] [PMID: 9695921]
4.  Oliveira, T.F., Vonrhein, C., Matias, P.M., Venceslau, S.S., Pereira, I.A. and Archer, M. The crystal structure of Desulfovibrio vulgaris dissimilatory sulfite reductase bound to DsrC provides novel insights into the mechanism of sulfate respiration. J. Biol. Chem. 283 (2008) 34141–34149. [DOI] [PMID: 18829451]
5.  Venceslau, S.S., Stockdreher, Y., Dahl, C. and Pereira, I.A. The "bacterial heterodisulfide" DsrC is a key protein in dissimilatory sulfur metabolism. Biochim. Biophys. Acta 1837 (2014) 1148–1164. [DOI] [PMID: 24662917]
6.  Loffler, M., Feldhues, J., Venceslau, S.S., Kammler, L., Grein, F., Pereira, I.AC. and Dahl, C. DsrL mediates electron transfer between NADH and rDsrAB in Allochromatium vinosum. Environ. Microbiol. 22 (2020) 783–795. [DOI] [PMID: 31854015]
[EC 1.8.1.22 created 2015 as EC 1.8.99.5, transferred 2023 to EC 1.8.1.22 ]
 
 
EC 1.8.5.10
Accepted name: [DsrC]-trisulfide reductase
Reaction: hydrogen sulfide + a [DsrC protein]-dithiol + 2 quinone = a [DsrC protein]-trisulfide + 2 quinol
Other name(s): DsrMKJOP complex
Systematic name: hydrogen sulfide:[DsrC protein]-dithiol oxidoreductase (trisulfide-forming)
Comments: This enzyme complex is present in both sulfate-reducing bacteria and sulfur-oxidizing bacteria, and acts in opposite directions during the reductive and oxidative pathways, respectively. DsrM and DsrP contain b-type hemes, DsrJ contains c-type hemes, DsrO is a ferredoxin-like protein, and DsrK is the catalytic subunit that acts as a disulfide reductase on DsrC proteins that contain a trisulfide bridge [1,3,4]. The complex receives the electrons from the membrane quinone pool [2,3].
Links to other databases: BRENDA, EXPASY, KEGG
References:
1.  Pott, A.S. and Dahl, C. Sirohaem sulfite reductase and other proteins encoded by genes at the dsr locus of Chromatium vinosum are involved in the oxidation of intracellular sulfur. Microbiology (Reading) 144 (1998) 1881–1894. [DOI] [PMID: 9695921]
2.  Pires, R.H., Venceslau, S.S., Morais, F., Teixeira, M., Xavier, A.V. and Pereira, I.A. Characterization of the Desulfovibrio desulfuricans ATCC 27774 DsrMKJOP complex - a membrane-bound redox complex involved in the sulfate respiratory pathway. Biochemistry 45 (2006) 249–262. [DOI] [PMID: 16388601]
3.  Grein, F., Pereira, I.A. and Dahl, C. Biochemical characterization of individual components of the Allochromatium vinosum DsrMKJOP transmembrane complex aids understanding of complex function in vivo. J. Bacteriol. 192 (2010) 6369–6377. [DOI] [PMID: 20952577]
4.  Santos, A.A., Venceslau, S.S., Grein, F., Leavitt, W.D., Dahl, C., Johnston, D.T. and Pereira, I.A. A protein trisulfide couples dissimilatory sulfate reduction to energy conservation. Science 350 (2015) 1541–1545. [DOI] [PMID: 26680199]
[EC 1.8.5.10 created 2023]
 
 
EC 1.8.99.5
Transferred entry: dissimilatory sulfite reductase. Now classified as EC 1.8.1.22, dissimilatory sulfite reductase system.
[EC 1.8.99.5 created 2015, deleted 2023]
 
 
*EC 2.1.1.298
Accepted name: ribosomal protein uL3 N5-glutamine methyltransferase
Reaction: S-adenosyl-L-methionine + [ribosomal protein uL3]-L-glutamine = S-adenosyl-L-homocysteine + [ribosomal protein uL3]-N5-methyl-L-glutamine
Other name(s): YfcB; PrmB
Systematic name: S-adenosyl-L-methionine:[ribosomal protein uL3]-L-glutamine (N5-glutamine)-methyltransferase
Comments: Modifies the glutamine residue in the glycylglycylglutamine (GGQ) motif of ribosomal protein uL3 (Gln150 in the protein from the bacterium Escherichia coli). The enzyme does not act on peptide chain release factor 1 or 2.
Links to other databases: BRENDA, EXPASY, KEGG
References:
1.  Heurgue-Hamard, V., Champ, S., Engstrom, A., Ehrenberg, M. and Buckingham, R.H. The hemK gene in Escherichia coli encodes the N5-glutamine methyltransferase that modifies peptide release factors. EMBO J. 21 (2002) 769–778. [DOI] [PMID: 11847124]
[EC 2.1.1.298 created 2014, modified 2023]
 
 
EC 2.1.1.391
Accepted name: demethylgadusol O-methyltransferase
Reaction: S-adenosyl-L-methionine + demethylgadusol = S-adenosyl-L-homocysteine + gadusol
Glossary: demethylgadusol = (4R,5R)-2,3,4,5-tetrahydroxy-5-(hydroxymethyl)cyclohex-2-en-1-one
gadusol = (4R,5R)-3,4,5-trihydroxy-5-(hydroxymethyl)-2-methoxycyclohex-2-en-1-one
Other name(s): gadusol synthase; desmethyl gadusol O-methyltransferase
Systematic name: S-adenosyl-L-methionine:demethylgadusol 2-O-methyltransferase
Comments: The enzyme, present in egg-laying vertebrates, is involved in biosynthesis of the UV absorbing compound gadusol. It is a bifunctional enzyme that also catalyses EC 1.3.1.126, 2-epi-5-epi-valiolone dehydrogenase.
Links to other databases: BRENDA, EXPASY, KEGG
References:
1.  Osborn, A.R., Almabruk, K.H., Holzwarth, G., Asamizu, S., LaDu, J., Kean, K.M., Karplus, P.A., Tanguay, R.L., Bakalinsky, A.T. and Mahmud, T. De novo synthesis of a sunscreen compound in vertebrates. Elife 4 (2015) . [DOI] [PMID: 25965179]
[EC 2.1.1.391 created 2023]
 
 
*EC 2.3.1.266
Accepted name: [ribosomal protein bS18]-alanine N-acetyltransferase
Reaction: acetyl-CoA + an N-terminal L-alanyl-[bS18 protein of 30S ribosome] = CoA + an N-terminal N-acetyl-L-alanyl-[bS18 protein of 30S ribosome]
Other name(s): rimI (gene name)
Systematic name: acetyl-CoA:N-terminal L-alanyl-[bS18 protein of 30S ribosome] N-acetyltransferase
Comments: The enzyme, characterized from bacteria, is specific for protein bS18, a component of the 30S ribosomal subunit. cf. EC 2.3.1.267, [ribosomal protein uS5]-alanine N-acetyltransferase.
Links to other databases: BRENDA, EXPASY, KEGG, PDB
References:
1.  Isono, K. and Isono, S. Ribosomal protein modification in Escherichia coli. II. Studies of a mutant lacking the N-terminal acetylation of protein S18. Mol. Gen. Genet. 177 (1980) 645–651. [DOI] [PMID: 6991870]
2.  Yoshikawa, A., Isono, S., Sheback, A. and Isono, K. Cloning and nucleotide sequencing of the genes rimI and rimJ which encode enzymes acetylating ribosomal proteins S18 and S5 of Escherichia coli K12. Mol. Gen. Genet. 209 (1987) 481–488. [DOI] [PMID: 2828880]
[EC 2.3.1.266 created 1990 as EC 2.3.1.128, part transferred 2018 to EC 2.3.1.266, modified 2023]
 
 
*EC 2.3.1.267
Accepted name: [ribosomal protein uS5]-alanine N-acetyltransferase
Reaction: acetyl-CoA + an N-terminal L-alanyl-[uS5 protein of 30S ribosome] = CoA + an N-terminal N-acetyl-L-alanyl-[uS5 protein of 30S ribosome]
Other name(s): rimJ (gene name)
Systematic name: acetyl-CoA:N-terminal L-alanyl-[uS5 protein of 30S ribosome] N-acetyltransferase
Comments: The enzyme, characterized from bacteria, is specific for protein uS5, a component of the 30S ribosomal subunit. It also plays a role in maturation of the 30S ribosomal subunit. cf. EC 2.3.1.266, [ribosomal protein bS18]-alanine N-acetyltransferase.
Links to other databases: BRENDA, EXPASY, KEGG
References:
1.  Yoshikawa, A., Isono, S., Sheback, A. and Isono, K. Cloning and nucleotide sequencing of the genes rimI and rimJ which encode enzymes acetylating ribosomal proteins S18 and S5 of Escherichia coli K12. Mol. Gen. Genet. 209 (1987) 481–488. [DOI] [PMID: 2828880]
2.  Roy-Chaudhuri, B., Kirthi, N., Kelley, T. and Culver, G.M. Suppression of a cold-sensitive mutation in ribosomal protein S5 reveals a role for RimJ in ribosome biogenesis. Mol. Microbiol. 68 (2008) 1547–1559. [DOI] [PMID: 18466225]
3.  Roy-Chaudhuri, B., Kirthi, N. and Culver, G.M. Appropriate maturation and folding of 16S rRNA during 30S subunit biogenesis are critical for translational fidelity. Proc. Natl. Acad. Sci. USA 107 (2010) 4567–4572. [DOI] [PMID: 20176963]
[EC 2.3.1.267 created 1990 as EC 2.3.1.128, part transferred 2018 to EC 2.3.1.267, modified 2023]
 
 
EC 2.3.3.22
Accepted name: 3-carboxymethyl-3-hydroxy-acyl-[acp] synthase
Reaction: an acetyl-[acp] + a 3-oxoacyl-[acp] = a 3-carboxymethyl-3-hydroxy-acyl-[acp] + [acp]
Other name(s): HMG-CoA synthase-like enzyme; aprE (gene name); curD (gene name); corE (gene name); bryR (gene name); pedP (gene name); 3-carboxymethyl-3-hydroxy-acyl-[acyl-carrier protein] synthase
Systematic name: acetyl-[acp]:3-oxoacyl-[acp] C-acetyltransferase (thioester-hydrolysing, carboxymethyl-forming)
Comments: This family of enzymes participates in a process that introduces a methyl branch into nascent polyketide products. The process begins with EC 4.1.1.124, malonyl-[acp] decarboxylase, which converts the common extender unit malonyl-[acp] to acetyl-[acp]. The enzyme is a mutated form of a ketosynthase enzyme, in which a Cys residue in the active site is modified to a Ser residue, leaving the decarboxylase function intact, but nulifying the ability of the enzyme to form a carbon-carbon bond. Next, EC 2.3.3.22, 3-carboxymethyl-3-hydroxy-acyl-[acp] synthase, utilizes the acetyl group to introduce the branch at the β position of 3-oxoacyl intermediates attached to a polyketide synthase, forming a 3-hydroxy-3-carboxymethyl intermediate. This is followed by dehydration catalysed by EC 4.2.1.181, 3-carboxymethyl-3-hydroxy-acyl-[acp] dehydratase (often referred to as an ECH1 domain), leaving a 3-carboxymethyl group and forming a double bond between the α and β carbons. The process concludes with decarboxylation catalysed by EC 4.1.1.125, 4-carboxy-3-alkylbut-2-enoyl-[acp] decarboxylase (often referred to as an ECH2 domain), leaving a methyl branch at the β carbon. The enzymes are usually encoded by a cluster of genes referred to as an "HMGS cassette", based on the similarity of the key enzyme to EC 2.3.3.10, hydroxymethylglutaryl-CoA synthase. While the enzyme is similar to EC 2.3.3.10, it is specific for an [acyl-carrier protein] (acp)-bound donor and does not interact with a CoA substrate as donor.
Links to other databases: BRENDA, EXPASY, KEGG
References:
1.  Erol, O., Schaberle, T.F., Schmitz, A., Rachid, S., Gurgui, C., El Omari, M., Lohr, F., Kehraus, S., Piel, J., Muller, R. and Konig, G.M. Biosynthesis of the myxobacterial antibiotic corallopyronin A. Chembiochem 11 (2010) 1253–1265. [DOI] [PMID: 20503218]
2.  Buchholz, T.J., Rath, C.M., Lopanik, N.B., Gardner, N.P., Hakansson, K. and Sherman, D.H. Polyketide β-branching in bryostatin biosynthesis: identification of surrogate acetyl-ACP donors for BryR, an HMG-ACP synthase. Chem. Biol. 17 (2010) 1092–1100. [DOI] [PMID: 21035732]
3.  Grindberg, R.V., Ishoey, T., Brinza, D., Esquenazi, E., Coates, R.C., Liu, W.T., Gerwick, L., Dorrestein, P.C., Pevzner, P., Lasken, R. and Gerwick, W.H. Single cell genome amplification accelerates identification of the apratoxin biosynthetic pathway from a complex microbial assemblage. PLoS One 6:e18565 (2011). [DOI] [PMID: 21533272]
4.  Maloney, F.P., Gerwick, L., Gerwick, W.H., Sherman, D.H. and Smith, J.L. Anatomy of the β-branching enzyme of polyketide biosynthesis and its interaction with an acyl-ACP substrate. Proc. Natl. Acad. Sci. USA 113 (2016) 10316–10321. [DOI] [PMID: 27573844]
5.  Slocum, S.T., Lowell, A.N., Tripathi, A., Shende, V.V., Smith, J.L. and Sherman, D.H. Chemoenzymatic dissection of polyketide β-branching in the bryostatin pathway. Methods Enzymol. 604 (2018) 207–236. [DOI] [PMID: 29779653]
[EC 2.3.3.22 created 2023]
 
 
EC 2.4.1.129
Transferred entry: peptidoglycan glycosyltransferase. Now EC 2.4.99.28, peptidoglycan glycosyltransferase
[EC 2.4.1.129 created 1984, modified 2002, deleted 2023]
 
 
EC 2.4.1.394
Accepted name: 4,6-α-glucanotransferase (linear substrates/linear products)
Reaction: formation of a linear isomalto/malto-polysaccharide from linear malto-oligosaccharides
Other name(s): gtfB (gene name) (ambiguous); gtfC (gene name)
Systematic name: linear (1→4)-α-D-glucan:(1→4)/(1→6)-α-D-glucan 6-α-D-glucosyltransferase
Comments: The enzyme, originally discovered in lactic acid bacteria but later found in other organisms, is similar to EC 2.4.1.395, reuteransucrase, yet is not able to act on sucrose. The enzyme, which belongs to the glycoside hydrolase 70 (GH70) family, possesses both hydrolase and transglycosylase activities, cleaving α(1→4) linkages from the non-reducing end of linear maltooligosaccharides and synthesizing linear α(1→6)-glucan chains. It also possesses an endo-α(1→4)-glycosidase activity. Due to its narrow binding groove, it is not able to act on branched substrates. cf. EC 2.4.1.396, 4,6-α-glucanotransferase (linear and branched substrates, branched products).
Links to other databases: BRENDA, EXPASY, KEGG
References:
1.  Kralj, S., van Geel-Schutten, G.H., Dondorff, M.MG., Kirsanovs, S., van der Maarel, M.JE.C. and Dijkhuizen, L. Glucan synthesis in the genus Lactobacillus: isolation and characterization of glucansucrase genes, enzymes and glucan products from six different strains. Microbiology (Reading) 150 (2004) 3681–3690. [DOI] [PMID: 15528655]
2.  Kralj, S., Grijpstra, P., van Leeuwen, S.S., Leemhuis, H., Dobruchowska, J.M., van der Kaaij, R.M., Malik, A., Oetari, A., Kamerling, J.P. and Dijkhuizen, L. 4,6-α-glucanotransferase, a novel enzyme that structurally and functionally provides an evolutionary link between glycoside hydrolase enzyme families 13 and 70. Appl. Environ. Microbiol. 77 (2011) 8154–8163. [DOI] [PMID: 21948833]
3.  Dobruchowska, J.M., Gerwig, G.J., Kralj, S., Grijpstra, P., Leemhuis, H., Dijkhuizen, L. and Kamerling, J.P. Structural characterization of linear isomalto-/malto-oligomer products synthesized by the novel GTFB 4,6-α-glucanotransferase enzyme from Lactobacillus reuteri 121. Glycobiology 22 (2012) 517–528. [DOI] [PMID: 22138321]
4.  Leemhuis, H., Dijkman, W.P., Dobruchowska, J.M., Pijning, T., Grijpstra, P., Kralj, S., Kamerling, J.P. and Dijkhuizen, L. 4,6-α-Glucanotransferase activity occurs more widespread in Lactobacillus strains and constitutes a separate GH70 subfamily. Appl. Microbiol. Biotechnol. 97 (2013) 181–193. [DOI] [PMID: 22361861]
5.  Gangoiti, J., Pijning, T. and Dijkhuizen, L. The Exiguobacterium sibiricum 255-15 GtfC enzyme represents a novel glycoside hydrolase 70 subfamily of 4,6-α-glucanotransferase enzymes. Appl. Environ. Microbiol. 82 (2016) 756–766. [DOI] [PMID: 26590275]
6.  Bai, Y., Gangoiti, J., Dijkstra, B.W., Dijkhuizen, L. and Pijning, T. Crystal structure of 4,6-α-glucanotransferase supports diet-driven evolution of GH70 enzymes from α-amylases in oral bacteria. Structure 25 (2017) 231–242. [DOI] [PMID: 28065507]
7.  Te Poele, E.M., van der Hoek, S.E., Chatziioannou, A.C., Gerwig, G.J., Duisterwinkel, W.J., Oudhuis, L.AA.CM., Gangoiti, J., Dijkhuizen, L. and Leemhuis, H. GtfC enzyme of Geobacillus sp. 12AMOR1 represents a novel thermostable type of GH70 4,6-α-glucanotransferase that synthesizes a linear alternating (α1→6)/(α1→4) α-glucan and delays bread staling. J. Agric. Food Chem. 69 (2021) 9859–9868. [DOI] [PMID: 34427087]
[EC 2.4.1.394 created 2023]
 
 
EC 2.4.1.395
Accepted name: reuteransucrase
Reaction: formation of reuteran from sucrose
Glossary: reuteran = a high-molecular-mass branched α-glucan produced by the lactic acid bacterium Limosilactobacillus reuteri.
Systematic name: sucrose:α-D-glucan 4-α/6-α-D-glucosyltransferase
Comments: The glucansucrases transfer a D-glucosyl residue from sucrose to a glucan chain. They are classified based on the linkage of the transferred glucosyl residue. The enzyme, characterized from the lactic acid bacterium Limosilactobacillus reuteri strain 121, catalyses the hydrolysis of sucrose and the transfer of the D-glucose moiety to suitable acceptors (inclduing sucrose), forming the glucan reuteran, which is typical for these strains. The enzyme forms mostly α(1→4) glucosidic linkages, but also α(1→6) linkages. The presence of maltose significantly accelerate the initial rate of the reaction. See EC 2.4.1.5, dextransucrase.
Links to other databases: BRENDA, EXPASY, KEGG
References:
1.  Kralj, S., van Geel-Schutten, G.H., Rahaoui, H., Leer, R.J., Faber, E.J., van der Maarel, M.J. and Dijkhuizen, L. Molecular characterization of a novel glucosyltransferase from Lactobacillus reuteri strain 121 synthesizing a unique, highly branched glucan with α-(1→4) and α-(1→6) glucosidic bonds. Appl. Environ. Microbiol. 68 (2002) 4283–4291. [DOI] [PMID: 12200277]
2.  Kralj, S., van Geel-Schutten, G.H., van der Maarel, M.JE.C. and Dijkhuizen, L. Biochemical and molecular characterization of Lactobacillus reuteri 121 reuteransucrase. Microbiology (Reading) 150 (2004) 2099–2112. [DOI] [PMID: 15256553]
3.  Kralj, S., Stripling, E., Sanders, P., van Geel-Schutten, G.H. and Dijkhuizen, L. Highly hydrolytic reuteransucrase from probiotic Lactobacillus reuteri strain ATCC 55730. Appl. Environ. Microbiol. 71 (2005) 3942–3950. [DOI] [PMID: 16000808]
[EC 2.4.1.395 created 2023]
 
 
EC 2.4.1.396
Accepted name: 4,6-α-glucanotransferase (linear and branched substrates, branched products)
Reaction: formation of a branched isomalto/malto-polysaccharide from branched malto-oligosaccharides
Other name(s): gtfB (gene name) (ambiguous); gtfD (gene name)
Systematic name: branched (1→4)-α-D-glucan:(1→4)/(1→6)-α-D-glucan 6-α-D-glucosyltransferase
Comments: The enzyme, discovered in several bacterial species, is similar to EC 2.4.1.395, reuteransucrase, yet is not able to act on sucrose. The enzyme, which belongs to the glycoside hydrolase 70 (GH70) family, possesses both hydrolase and transglycosylase activities, cleaving endo α(1→4) linkages from the non-reducing end of maltooligosaccharides and adding the resulting oligosaccharides to the non-reducing end of α-D-glucan chains that terminate with a residue linked by an α-(1→4) linkage, forming an α(1→6) linkage. The enzyme is not able to form successive α(1→6) linkages. Unlike EC 2.4.1.394, 4,6-α-glucanotransferase (linear substrates/linear products), which can only act on linear substrates, this enzyme is able to act on both linear and branched substrates, and can form the branched reuteran type of α-glucan.
Links to other databases: BRENDA, EXPASY, KEGG
References:
1.  Gangoiti, J., van Leeuwen, S.S., Vafiadi, C. and Dijkhuizen, L. The Gram-negative bacterium Azotobacter chroococcum NCIMB 8003 employs a new glycoside hydrolase family 70 4,6-α-glucanotransferase enzyme (GtfD) to synthesize a reuteran like polymer from maltodextrins and starch. Biochim. Biophys Acta 1860 (2016) 1224–1236. [DOI] [PMID: 26868718]
2.  Gangoiti, J., van Leeuwen, S.S., Meng, X., Duboux, S., Vafiadi, C., Pijning, T. and Dijkhuizen, L. Mining novel starch-converting glycoside hydrolase 70 enzymes from the Nestle Culture Collection genome database: the Lactobacillus reuteri NCC 2613 GtfB. Sci. Rep. 7:9947 (2017). [DOI] [PMID: 28855510]
3.  Pijning, T., Gangoiti, J., Te Poele, E.M., Borner, T. and Dijkhuizen, L. Insights into broad-specificity starch modification from the crystal structure of Limosilactobacillus reuteri NCC 2613 4,6-α-glucanotransferase GtfB. J. Agric. Food Chem. 69 (2021) 13235–13245. [DOI] [PMID: 34708648]
[EC 2.4.1.396 created 2023]
 
 
EC 2.4.99.28
Accepted name: peptidoglycan glycosyltransferase
Reaction: [GlcNAc-(1→4)-Mur2Ac(oyl-L-Ala-γ-D-Glu-L-Lys-D-Ala-D-Ala)]n-diphosphoundecaprenol + GlcNAc-(1→4)-Mur2Ac(oyl-L-Ala-γ-D-Glu-L-Lys-D-Ala-D-Ala)-diphosphoundecaprenol = [GlcNAc-(1→4)-Mur2Ac(oyl-L-Ala-γ-D-Glu-L-Lys-D-Ala-D-Ala)]n+1-diphosphoundecaprenol + undecaprenyl diphosphate
Glossary: Mur2Ac = N-acetylmuramic acid
Other name(s): PG-II; bactoprenyldiphospho-N-acetylmuramoyl-(N-acetyl-D-glucosaminyl)-pentapeptide:peptidoglycan N-acetylmuramoyl-N-acetyl-D-glucosaminyltransferase; penicillin binding protein (3 or 1B); peptidoglycan transglycosylase; undecaprenyldiphospho-(N-acetyl-D-glucosaminyl-(1→4)-N-acetyl-D-muramoylpentapeptide):undecaprenyldiphospho-(N-acetyl-D-glucosaminyl-(1→4)-N-acetyl-D-muramoylpentapeptide) disaccharidetransferase
Systematic name: [poly-N-acetyl-D-glucosaminyl-(1→4)-(N-acetyl-D-muramoylpentapeptide)]-diphosphoundecaprenol:[N-acetyl-D-glucosaminyl-(1→4)-N-acetyl-D-muramoylpentapeptide]-diphosphoundecaprenol disaccharidetransferase
Comments: The enzyme also works when the lysine residue is replaced by meso-2,6-diaminoheptanedioate (meso-2,6-diaminopimelate, A2pm) combined with adjacent residues through its L-centre, as it is in Gram-negative and some Gram-positive organisms. The undecaprenol involved is ditrans,octacis-undecaprenol (for definitions, click here). Involved in the synthesis of cell-wall peptidoglycan.
Links to other databases: BRENDA, EXPASY, KEGG, PDB, CAS registry number: 79079-04-2
References:
1.  Taku, A., Stuckey, M. and Fan, D.P. Purification of the peptidoglycan transglycosylase of Bacillus megaterium. J. Biol. Chem. 257 (1982) 5018–5022. [DOI] [PMID: 6802846]
2.  Goffin, C. and Ghuysen, J.-M. Multimodular penicillin-binding proteins: an enigmatic family of orthologs and paralogs. Microbiol. Mol. Biol. Rev. 62 (1998) 1079–1093. [DOI] [PMID: 9841666]
3.  van Heijenoort, J. Formation of the glycan chains in the synthesis of bacterial peptidoglycan. Glycobiology 11 (2001) 25. [DOI] [PMID: 11320055]
[EC 2.4.99.28 created 1984 as EC 2.4.1.129, modified 2002, transferred 2023 to EC 2.4.99.28]
 
 
*EC 2.8.4.4
Accepted name: [ribosomal protein uS12] (aspartate89-C3)-methylthiotransferase
Reaction: L-aspartate89-[ribosomal protein uS12] + sulfur-(sulfur carrier) + 2 S-adenosyl-L-methionine + reduced acceptor = 3-(methylsulfanyl)-L-aspartate89-[ribosomal protein uS12] + S-adenosyl-L-homocysteine + (sulfur carrier) + L-methionine + 5′-deoxyadenosine + oxidized acceptor (overall reaction)
(1a) S-adenosyl-L-methionine + L-aspartate89-[ribosomal protein uS12] + sulfur-(sulfur carrier) = S-adenosyl-L-homocysteine + L-aspartate89-[ribosomal protein uS12]-methanethiol + (sulfur carrier)
(1b) L-aspartate89-[ribosomal protein uS12]-methanethiol + S-adenosyl-L-methionine + reduced acceptor = 3-(methylsulfanyl)-L-aspartate89-[ribosomal protein uS12] + L-methionine + 5′-deoxyadenosine + oxidized acceptor
Other name(s): RimO; [ribosomal protein S12]-Asp89:sulfur-(sulfur carrier),S-adenosyl-L-methionine C3-methylthiotransferase; [ribosomal protein S12]-L-aspartate89:sulfur-(sulfur carrier),S-adenosyl-L-methionine C3-methylthiotransferase
Systematic name: [ribosomal protein uS12]-L-aspartate89:sulfur-(sulfur carrier),S-adenosyl-L-methionine C3-(methylsulfanyl)transferase
Comments: This bacterial enzyme binds two [4Fe-4S] clusters [2,3]. A bridge of five sulfur atoms is formed between the free Fe atoms of the two [4Fe-4S] clusters [6]. In the first reaction the enzyme transfers a methyl group from AdoMet to the external sulfur ion of the sulfur bridge. In the second reaction the enzyme catalyses the reductive fragmentation of a second molecule of AdoMet, yielding a 5′-deoxyadenosine radical, which then attacks the methylated sulfur atom of the polysulfide bridge, resulting in the transfer of a methylsulfanyl group to aspartate89 [5,6]. The enzyme is a member of the superfamily of S-adenosyl-L-methionine-dependent radical (radical AdoMet) enzymes.
Links to other databases: BRENDA, EXPASY, KEGG, PDB
References:
1.  Anton, B.P., Saleh, L., Benner, J.S., Raleigh, E.A., Kasif, S. and Roberts, R.J. RimO, a MiaB-like enzyme, methylthiolates the universally conserved Asp88 residue of ribosomal protein S12 in Escherichia coli. Proc. Natl. Acad. Sci. USA 105 (2008) 1826–1831. [DOI] [PMID: 18252828]
2.  Lee, K.H., Saleh, L., Anton, B.P., Madinger, C.L., Benner, J.S., Iwig, D.F., Roberts, R.J., Krebs, C. and Booker, S.J. Characterization of RimO, a new member of the methylthiotransferase subclass of the radical SAM superfamily. Biochemistry 48 (2009) 10162–10174. [DOI] [PMID: 19736993]
3.  Arragain, S., Garcia-Serres, R., Blondin, G., Douki, T., Clemancey, M., Latour, J.M., Forouhar, F., Neely, H., Montelione, G.T., Hunt, J.F., Mulliez, E., Fontecave, M. and Atta, M. Post-translational modification of ribosomal proteins: structural and functional characterization of RimO from Thermotoga maritima, a radical S-adenosylmethionine methylthiotransferase. J. Biol. Chem. 285 (2010) 5792–5801. [DOI] [PMID: 20007320]
4.  Strader, M.B., Costantino, N., Elkins, C.A., Chen, C.Y., Patel, I., Makusky, A.J., Choy, J.S., Court, D.L., Markey, S.P. and Kowalak, J.A. A proteomic and transcriptomic approach reveals new insight into β-methylthiolation of Escherichia coli ribosomal protein S12. Mol. Cell. Proteomics 10:M110.005199 (2011). [DOI] [PMID: 21169565]
5.  Landgraf, B.J., Arcinas, A.J., Lee, K.H. and Booker, S.J. Identification of an intermediate methyl carrier in the radical S-adenosylmethionine methylthiotransferases RimO and MiaB. J. Am. Chem. Soc. 135 (2013) 15404–15416. [DOI] [PMID: 23991893]
6.  Forouhar, F., Arragain, S., Atta, M., Gambarelli, S., Mouesca, J.M., Hussain, M., Xiao, R., Kieffer-Jaquinod, S., Seetharaman, J., Acton, T.B., Montelione, G.T., Mulliez, E., Hunt, J.F. and Fontecave, M. Two Fe-S clusters catalyze sulfur insertion by radical-SAM methylthiotransferases. Nat. Chem. Biol. 9 (2013) 333–338. [DOI] [PMID: 23542644]
[EC 2.8.4.4 created 2014, modified 2014, modified 2023]
 
 
EC 3.1.1.122
Accepted name: carbendazim hydrolysing esterase
Reaction: carbendazim + H2O = 2-aminobenzimidazole + CO2 + methanol (overall reaction)
(1a) carbendazim + H2O = N-(1H-1,3-benzodiazol-2-yl)carbamate + methanol
(1b) N-(1H-1,3-benzodiazol-2-yl)carbamate = 2-aminobenzimidazole + CO2 (spontaneous)
Glossary: carbendazim = methyl 1H-benzimidazol-2-ylcarbamate; 2-aminobenzimidazole = 1H-benzimidazol-2-amine
Other name(s): mheI (gene name)
Systematic name: carbendazim methanol hydrolase (decarboxylating)
Comments: The enzyme, which is inducible in the soil bacterium Nocardioides sp. (strain SG-4G), catalyses the degradation of the fungicide carbendazim. Following hydrolysis of the carbamate ester, the carbamate decarboxylates spontaneously.
Links to other databases: BRENDA, EXPASY, KEGG, CAS registry number: 10605-21-7
References:
1.  Pandey, G., Dorrian, S.J., Russell, R.J., Brearley, C., Kotsonis, S. and Oakeshott, J.G. Cloning and biochemical characterization of a novel carbendazim (methyl-1H-benzimidazol-2-ylcarbamate)-hydrolyzing esterase from the newly isolated Nocardioides sp. strain SG-4G and its potential for use in enzymatic bioremediation. Appl. Environ. Microbiol. 76 (2010) 2940–2945. [DOI] [PMID: 20228105]
[EC 3.1.1.122 created 2023]
 
 
*EC 3.1.3.62
Accepted name: multiple inositol-polyphosphate phosphatase
Reaction: (1) myo-inositol hexakisphosphate + H2O = 1D-myo-inositol 1,2,4,5,6-pentakisphosphate + phosphate
(2) 1D-myo-inositol 1,2,4,5,6-pentakisphosphate + H2O = 1D-myo-inositol 1,2,5,6-tetrakisphosphate + phosphate
(3) 1D-myo-inositol 1,2,5,6-tetrakisphosphate + H2O = 1D-myo-inositol 1,2,6-trisphosphate + phosphate
(4) 1D-myo-inositol 1,2,6-trisphosphate + H2O = 1D-myo-inositol 1,2-bisphosphate + phosphate
(5) 1D-myo-inositol 1,2-bisphosphate + H2O = 1D-myo-inositol 2-phosphate + phosphate
Glossary: myo-inositol hexakisphosphate = phytate
1D-myo-inositol 1,3,4,5,6-pentakisphosphate = Ins(1,3,4,5,6)P5
1D-myo-inositol 1,3,4,5-tetrakisphosphate = Ins(1,3,4,5)P4
1D-myo-inositol 1,4,5,6-tetrakisphosphate = Ins(1,4,5,6)P4
1D-myo-inositol 1,4,5-trisphosphate = Ins(1,4,5)P3
1D-myo-inositol 2,3-bisphosphate = Ins(2,3)P2
1D-myo-inositol 2-phosphate = Ins(2)P
Other name(s): MIPP; phytase (ambiguous); 1D-myo-inositol-hexakisphosphate 5-phosphohydrolase (incorrect)
Systematic name: myo-inositol-hexakisphosphate phosphohydrolase
Comments: This ubiquitous enzyme degrades myo-inositol hexakisphosphate (phytate) to Ins(2,3)P2 and Ins(2)P. Activities have been characterized in the yeast Saccharomyces cerevisiae [2], the plant Lupinus albus [3] and the bacteria Bacillus sp. [4] and Raoultella terrigena [5]. In mammal cells Ins(2,3)P2 and Ins(2)P are the major inositol phosphate compounds found [6]. The mammal enzyme is also active on Ins(1,3,4,5,6)P5 that is dephosphorylated to Ins(1,4,5,6)P4 and Ins(1,4,5)P3, and on 2,3-bisphospho-D-glycerate (cf. EC 3.1.3.80, 2,3-bisphosphoglycerate 3-phosphatase). In addition, it acts on Ins(1,3,4,5)P4 to yield Ins(1,4,5)P3 in vitro (cf. EC 3.1.3.67, phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase) [7]. It does not hydrolyse phosphates from the 2-positions of inositol phosphates [6]. In other organisms the degradation of phytate follows different routes. (cf. EC 3.1.3.8, 3-phytase, EC 3.1.3.26, 4-phytase, and EC 3.1.3.72, 5-phytase).
Links to other databases: BRENDA, EXPASY, KEGG, PDB, CAS registry number: 116958-30-6
References:
1.  Craxton, A., Caffrey, J.J., Burkhart, W., Safrany, S.T. and Shears, S.B. Molecular cloning and expression of a rat hepatic multiple inositol polyphosphate phosphatase. Biochem. J. 328 (1997) 75–81. [DOI] [PMID: 9359836]
2.  Greiner, R., Alminger, M.L. and Carlsson, N.G. Stereospecificity of myo-inositol hexakisphosphate dephosphorylation by a phytate-degrading enzyme of baker’s yeast. J. Agric. Food Chem. 49 (2001) 2228–2233. [DOI] [PMID: 11368581]
3.  Greiner, R., Larsson Alminger, M., Carlsson, N.G., Muzquiz, M., Burbano, C., Cuadrado, C., Pedrosa, M.M. and Goyoaga, C. Pathway of dephosphorylation of myo-inositol hexakisphosphate by phytases of legume seeds. J. Agric. Food Chem. 50 (2002) 6865–6870. [DOI] [PMID: 12405789]
4.  Greiner, R., Farouk, A., Alminger, M.L. and Carlsson, N.G. The pathway of dephosphorylation of myo-inositol hexakisphosphate by phytate-degrading enzymes of different Bacillus spp. Can. J. Microbiol. 48 (2002) 986–994. [DOI] [PMID: 12556126]
5.  Greiner, R. and Carlsson, N.G. myo-Inositol phosphate isomers generated by the action of a phytate-degrading enzyme from Klebsiella terrigena on phytate. Can. J. Microbiol. 52 (2006) 759–768. [DOI] [PMID: 16917535]
6.  Nguyen Trung, M., Kieninger, S., Fandi, Z., Qiu, D., Liu, G., Mehendale, N.K., Saiardi, A., Jessen, H., Keller, B. and Fiedler, D. Stable isotopomers of myo-inositol uncover a complex MINPP1-dependent inositol phosphate network. ACS Cent. Sci. 8 (2022) 1683–1694. [DOI] [PMID: 36589890]
7.  Yu, J., Leibiger, B., Yang, S.N., Shears, S.B., Leibiger, I.B., Berggren, P.O. and Barker, C.J. Multiple inositol polyphosphate phosphatase compartmentalization separates inositol phosphate metabolism from inositol lipid signaling. Biomolecules 13 (2023) . [DOI] [PMID: 37371464]
[EC 3.1.3.62 created 1992, modified 2002, modified 2023]
 
 
EC 3.1.8.2
Transferred entry: diisopropyl-fluorophosphatase. Now classified as EC 3.8.2.2, diisopropyl-fluorophosphatase
[EC 3.1.8.2 created 1961 as EC 3.8.2.1, transferred 1992 to EC 3.1.8.2, deleted 2023]
 
 
EC 3.2.1.221
Accepted name: MMP endo-(1,4)-3-O-methyl-α-D-mannosidase
Reaction: Endohydrolysis of 3-O-methyl-α-D-mannosyl-(1→4)-3-O-methyl-D-mannose linkages within (1,4)-3-O-methyl-α-D-mannnan substrates
Glossary: MMP = 3-O-methylmannose polysaccharide = α-D-mannosyl-(1→4)-[3-O-methyl-α-D-mannosyl-(1→4)]n-1-O,3-O-dimethyl-α-D-mannose
Other name(s): MMP α-(1→4)-endomannosidase; mmpH (gene name)
Systematic name: (1,4)-3-O-methyl-α-D-mannan 4-α-3-O-methyl-D-mannohydrolase
Comments: The enzyme, present in mycobacterial species that produce 3-O-methylmannose polysaccharide (MMP), is involved in recycling and biosynthesis of the polymer. The enzyme has been shown to cleave substrates in the range of 11–14 mannose residues.
Links to other databases: BRENDA, EXPASY, KEGG
References:
1.  Maranha, A., Costa, M., Ripoll-Rozada, J., Manso, J.A., Miranda, V., Mendes, V.M., Manadas, B., Macedo-Ribeiro, S., Ventura, M.R., Pereira, P.JB. and Empadinhas, N. Self-recycling and partially conservative replication of mycobacterial methylmannose polysaccharides. Commun Biol 6:108 (2023). [DOI] [PMID: 36707645]
[EC 3.2.1.221 created 2023]
 
 
EC 3.2.1.222
Accepted name: funoran endo-β-hydrolase
Reaction: Endohydrolysis of β-(1→4)-linkages between β-D-galactopyranose-6-sulfate and 3,6-anhydro-α-L-galactopyranose units in funoran
Glossary: funoran = [-3)-β-D-galactopyranose-6-sulfate-(1-4)-3,6-anhydro-α-L-galactopyranose-(1-]
Other name(s): β-funoranase
Systematic name: funoran endo β-(1,4)-glycanohydrolase
Comments: The enzyme is an endo hydrolase that hydrolyses the β(1,4) bond in funoran, a polysaccharide produced by red algae of the genus Gloiopeltis. The enzyme from the marine bacterium Wenyingzhuangia aestuarii OF219 acts on agarose with a higher efficiency (cf. EC 3.2.1.81, β-agarase), but binds funoran preferentially.
Links to other databases: BRENDA, EXPASY, KEGG
References:
1.  Zhang, Y., Chen, G., Shen, J., Mei, X., Liu, G., Chang, Y., Dong, S., Feng, Y., Wang, Y. and Xue, C. The characteristic structure of funoran could be hydrolyzed by a GH86 family enzyme (Aga86A_Wa): Discovery of the funoran hydrolase. Carbohyd Polym 318 (2023) 121117. [DOI]
[EC 3.2.1.222 created 2023]
 
 
EC 3.2.1.223
Accepted name: arabinogalactan exo α-(1,3)-β-L-arabinopyranosyl-(1→3)-L-arabinofuranosidase (non-reducing end)
Reaction: Hydrolysis of β-L-Arap-(1→3)-L-Araf disaccharides from non-reducing terminals in branches of type II arabinogalactan attached to proteins.
Glossary: Araf = arabinofuranose
Arap = arabinopyranose
Other name(s): 3-O-β-L-arabinopyranosyl-α-L-arabinofuranosidase; AAfase
Systematic name: type II arabinogalactan exo α-(1,3)-[β-L-arabinopyranosyl-(1→3)-L-arabinofuranose] hydrolase (non-reducing end)
Comments: The enzyme, characterized from the bacterium Bifidobacterium pseudocatenulatum, specifically hydrolyses β;-L-Arap-(1→3)-L-Araf disaccharides from the non-reducing terminal of arabinogalactan using an exo mode of action. It is active with arabinogalactan-proteins (AGPs) containing type II arabinogalactans such as gum arabic AGP and larch AGP. The enzyme can also hydrolyse α-D-Galp-(1→3)-L-Araf disaccharides (cf. EC 3.2.1.215) with a much lower activity.
Links to other databases: BRENDA, EXPASY, KEGG
References:
1.  Sasaki, Y., Yanagita, M., Hashiguchi, M., Horigome, A., Xiao, J. Z., Odamaki, T., Kitahara, K. and Fujita, K. Assimilation of arabinogalactan side chains with novel 3-O-β-L-arabinopyranosyl-α-L-arabinofuranosidase in Bifidobacterium pseudocatenulatum. Microbiome Res. Rep. 2:12 (2023). [DOI]
[EC 3.2.1.223 created 2023]
 
 
EC 3.4.21.123
Accepted name: kumamolysin
Reaction: The enzyme preferentially hydrolyses peptides having an Ala or Pro residue at P2 position and prefers such charged amino acid residues as Glu or Arg at the P2′ position. In the oxidized insulin B chain, kumamolysin preferentially cleaves between Leu15 and Tyr16
Other name(s): KSCP; kumamolisin
Comments: This bacterial pepstatin-insensitive carboxyl proteinase has been isolated and characterized from Bacillus sp. MN-32 and from several Burkholderia spp. Kumamolysin from Bacillus sp. MN-32 exhibits a Ser278/Glu78/Asp82 catalytic triad. The enzyme is a type example of peptidase family S53 in the MEROPS Peptidas Database.
Links to other databases: BRENDA, EXPASY, KEGG
References:
1.  Murao, S., Ohkuni, K., Nagao, M., Hirayama, K., Fukuhara, K., Oda, K., Oyama, H. and Shin, T. Purification and characterization of kumamolysin, a novel thermostable pepstatin-insensitive carboxyl proteinase from Bacillus novosp. MN-32. J. Biol. Chem. 268 (1993) 349–355. [PMID: 8416942]
2.  Oda, K., Ogasawara, S., Oyama, H. and Dunn, B.M. Subsite preferences of pepstatin-insensitive carboxyl proteinases from prokaryotes: kumamolysin, a thermostable pepstatin-insensitive carboxyl proteinase. J. Biochem. 128 (2000) 499–507. [DOI] [PMID: 10965051]
3.  Oyama, H., Hamada, T., Ogasawara, S., Uchida, K., Murao, S., Beyer, B.B., Dunn, B.M. and Oda, K. A CLN2-related and thermostable serine-carboxyl proteinase, kumamolysin: cloning, expression, and identification of catalytic serine residue. J. Biochem. 131 (2002) 757–765. [DOI] [PMID: 11983085]
4.  Comellas-Bigler, M., Fuentes-Prior, P., Maskos, K., Huber, R., Oyama, H., Uchida, K., Dunn, B.M., Oda, K. and Bode, W. The 1.4 a crystal structure of kumamolysin: a thermostable serine-carboxyl-type proteinase. Structure 10 (2002) 865–876. [DOI] [PMID: 12057200]
5.  Wlodawer, A., Li, M., Gustchina, A., Tsuruoka, N., Ashida, M., Minakata, H., Oyama, H., Oda, K., Nishino, T. and Nakayama, T. Crystallographic and biochemical investigations of kumamolisin-As, a serine-carboxyl peptidase with collagenase activity. J. Biol. Chem. 279 (2004) 21500–21510. [DOI] [PMID: 15014068]
[EC 3.4.21.123 created 2023]
 
 
*EC 3.4.24.84
Accepted name: Ste24 endopeptidase
Reaction: Hydrolyses the peptide bond -P2-(S-farnesyl or geranylgeranyl)C-P1′-P2′-P3′-COOH where P1′ and P2′ are amino acids with aliphatic side chains and P3′ is any C-terminal residue.
Comments: The enzyme hydrolyses proteins that terminate with a CaaX motif in which C is an S-isoprenylated cysteine residue, a is usually aliphatic and X is the C-terminal residue of the substrate protein, and may be any of several amino acids.The enzyme, which is the Type example of peptidase family M48, is one of two enzymes that can catalyse this processing step for mating a-factor in yeast. Subsequently, the S-isoprenylated cysteine residue that forms the new C-terminus is methyl-esterified and forms a hydrophobic membrane-anchor. Differs from EC 3.4.26.1, intramembrane prenyl-peptidase Rce1, in its catalytic mechanism and substrate preference.
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, PDB, CAS registry number: 148463-92-7
References:
1.  Fujimura-Kamada, K., Nouvet, F.J. and Michaelis, S. A novel membrane-associated metalloprotease, Ste24p, is required for the first step of NH2-terminal processing of the yeast a-factor precursor. J. Cell Biol. 136 (1997) 271–285. [DOI] [PMID: 9015299]
2.  Tam, A., Schmidt, W.K. and Michaelis, S. The multispanning membrane protein Ste24p catalyzes CAAX proteolysis and NH2-terminal processing of the yeast a-factor precursor. J. Biol. Chem. 276 (2001) 46798–46806. [DOI] [PMID: 11581258]
[EC 3.4.24.84 created 2003, modified 2023]
 
 
EC 3.4 Acting on peptide bonds (peptidases)
 
EC 3.4.26 Glutamic endopeptidases
 
EC 3.4.26.1
Accepted name: intramembrane prenyl-peptidase Rce1
Reaction: Hydrolyses the peptide bond -P2-(S-farnesyl or geranylgeranyl)C-P1′-P2′-P3′-COOH where where P1′ and P2′ are amino acids with aliphatic sidechains and P3′ is any C-terminal residue.
Other name(s): CaaX prenyl protease 2; prenyl protein-specific endoprotease 2; PPSEP 2; α-factor-converting enzyme RCE1; ras converting enzyme; RACE; glutamic-type intramembrane endopeptidase Rce1; type II CAAX protease.
Comments: The cleavage site motif is typically referred to as CaaX, where the letter a represents any amino acid, rather than alanine, and X represents the C-terminal amino acid of the target protein. The enzyme has been found in the yeast Saccharomyces cerevisiae and homologues exist in humans and several other species. Although the cleavage site is similar to that of the metallo-peptidase Ste24 endopeptidase (EC 3.4.24.84), there appear to be specificity differences in the proteins hydrolysed by these two enzymes, with amino-acid substitution studies indicating activity of the yeast enzyme towards substrates with a hydrophylic residue at (P1′) that are not hydrolysed by EC 3.4.24.84 [4].
Links to other databases: BRENDA, EXPASY, KEGG
References:
1.  Otto, J.C., Kim, E., Young, S.G. and Casey, P.J. Cloning and characterization of a mammalian prenyl protein-specific protease. J. Biol. Chem. 274 (1999) 8379–8382. [DOI] [PMID: 10085068]
2.  Manolaridis, I., Kulkarni, K., Dodd, R.B., Ogasawara, S., Zhang, Z., Bineva, G., Reilly, N.O., Hanrahan, S.J., Thompson, A.J., Cronin, N., Iwata, S. and Barford, D. Mechanism of farnesylated CAAX protein processing by the intramembrane protease Rce1. Nature 504 (2013) 301–305. [DOI] [PMID: 24291792]
3.  Pei, J., Mitchell, D.A., Dixon, J.E. and Grishin, N.V. Expansion of type II CAAX proteases reveals evolutionary origin of γ-secretase subunit APH-1. J. Mol. Biol. 410 (2011) 18–26. [DOI] [PMID: 21570408]
4.  Trueblood, C.E., Boyartchuk, V.L., Picologlou, E.A., Rozema, D., Poulter, C.D. and Rine, J. The CaaX proteases, Afc1p and Rce1p, have overlapping but distinct substrate specificities. Mol. Cell Biol. 20 (2000) 4381–4392. [DOI] [PMID: 10825201]
5.  Plummer, L.J., Hildebrandt, E.R., Porter, S.B., Rogers, V.A., McCracken, J. and Schmidt, W.K. Mutational analysis of the ras converting enzyme reveals a requirement for glutamate and histidine residues. J. Biol. Chem. 281 (2006) 4596–4605. [DOI] [PMID: 16361710]
[EC 3.4.26.1 created 2023]
 
 
EC 3.4.26.2
Accepted name: scytalidoglutamic peptidase
Reaction: Hydrolysis of proteins, with a strong preference for Phe or Tyr at position P1 and one of the smaller amino-acids at P1′ in the sequence - P3 - P2 - P1 ┼P1′- P2′- P3′-. Cleaves the Tyr26-Thr27 bond in the B chain of oxidized insulin, which is not cleaved by pepsin.
Other name(s): scytalidopepsin-B; SCP-B; SGP; scytalidocarboxylpeptidase-B
Comments: The enzyme, isolated from the fungus Scytalidium lignicola and found in several other fungi, has a low pH optimum, being most active at pH 2 with casein as substrate. It differs from the pepsins (EC 3.4.23.1 and EC 3.4.23.2) in being insensitive to inhibition by pepstatin. It also differs from mammalian pepsins in showing a preference for a positively charged residue ( Lys or Arg) at the P3 position. In addition to the catalytic Glu residue, a Gln residue appears to play an important role in the hydrolytic mechanism. A member of peptidase family G01, the "eqolisin" family of glutamic peptidases (G01.0001).
Links to other databases: BRENDA, EXPASY, KEGG
References:
1.  Kataoka, Y., Takada, K., Oyama, H., Tsunemi, M., James, M.N. and Oda, K. Catalytic residues and substrate specificity of scytalidoglutamic peptidase, the first member of the eqolisin in family (G1) of peptidases. FEBS Lett. 579 (2005) 2991–2994. [DOI] [PMID: 15907842]
2.  Fujinaga, M., Cherney, M.M., Oyama, H., Oda, K. and James, M.N. The molecular structure and catalytic mechanism of a novel carboxyl peptidase from Scytalidium lignicolum. Proc. Natl. Acad. Sci. USA 101 (2004) 3364–3369. [DOI] [PMID: 14993599]
3.  Pillai, B., Cherney, M.M., Hiraga, K., Takada, K., Oda, K. and James, M.N. Crystal structure of scytalidoglutamic peptidase with its first potent inhibitor provides insights into substrate specificity and catalysis. J. Mol. Biol. 365 (2007) 343–361. [DOI] [PMID: 17069854]
4.  Kondo, M.Y., Okamoto, D.N., Santos, J.A., Juliano, M.A., Oda, K., Pillai, B., James, M.N., Juliano, L. and Gouvea, I.E. Studies on the catalytic mechanism of a glutamic peptidase. J. Biol. Chem. 285 (2010) 21437–21445. [DOI] [PMID: 20442413]
[EC 3.4.26.2 created 2023]
 
 
*EC 3.5.1.12
Accepted name: biotinidase
Reaction: biocytin + H2O = biotin + L-lysine
Glossary: biocytin = ε-N-biotinyl-L-lysine
Other name(s): amidohydrolase biotinidase; biocytinase; biotin-amide amidohydrolase
Systematic name: biocytin amidohydrolase
Comments: The enzyme, found in many bacterial species as well as animals, liberates biotin from biocytin and short biotinylated peptides, but not from biotinylated proteins. It also has activity on biotin esters and biotin amides.
Links to other databases: BRENDA, EXPASY, KEGG, CAS registry number: 9025-15-4
References:
1.  Thoma, R.W. and Peterson, W.H. The enzymatic degradation of soluble bound biotin. J. Biol. Chem. 210 (1954) 569–579. [DOI] [PMID: 13211594]
2.  Knappe, J., Brümer, W. and Biederbick, K. Reinigung und Eigenschaften der Biotinidase aus Schweinenieren und Lactobacillus casei. Biochem. Z. 338 (1963) 599–613. [PMID: 14087327]
3.  Pispa, J. and Koivusalo, M. Actinomycin D-sensitive increase in the biotinidase activity in mouse liver and serum after ethionine feeding. Acta Chem. Scand. 26 (1972) 2133–2135. [DOI] [PMID: 5081874]
[EC 3.5.1.12 created 1961, modified 2023]
 
 
EC 3.8.2.2
Accepted name: diisopropyl-fluorophosphatase
Reaction: diisopropyl fluorophosphate + H2O = diisopropyl phosphate + fluoride
Other name(s): DFPase; tabunase; somanase; organophosphorus acid anhydrolase; organophosphate acid anhydrase; OPA anhydrase (ambiguous); diisopropylphosphofluoridase; dialkylfluorophosphatase; diisopropyl phosphorofluoridate hydrolase; isopropylphosphorofluoridase; diisopropylfluorophosphonate dehalogenase
Systematic name: diisopropyl-fluorophosphate fluorohydrolase
Comments: Acts on phosphorus anhydride bonds (such as phosphorus-halide and phosphorus-cyanide) in organophosphorus compounds (including ‘nerve gases’). Inhibited by chelating agents; requires divalent cations. Related to EC 3.1.8.1 aryldialkylphosphatase.
Links to other databases: BRENDA, EXPASY, KEGG, PDB, CAS registry number: 9032-18-2
References:
1.  Augustinsson, K.-B. and Heimburger, G. Enzymatic hydrolysis of organophosphorus compounds. I. Occurrence of enzymes hydrolysing dimethyl-amido-ethoxy-phosphoryl cyanide (Tabun). Acta Chem. Scand. 8 (1954) 753–761. [DOI]
2.  Augustinsson, K.-B. and Heimburger, G. Enzymatic hydrolysis of organophosphorus compounds. II. Analysis of reaction products in experiments with Tabun and some properties of blood plasma tabunase. Acta Chem. Scand. 8 (1954) 762–767. [DOI]
3.  Augustinsson, K.-B. and Heimburger, G. Enzymatic hydrolysis of organophosphorus compounds. IV. Specificity studies. Acta Chem. Scand. 8 (1954) 1533–1541. [DOI]
4.  Cohen, J.A. and Warringa, M.G.P.J. Purification and properties of dialkylfluorophosphatase. Biochim. Biophys. Acta 26 (1957) 29–39. [DOI] [PMID: 13479457]
5.  Mounter, L.A. Enzymic hydrolysis of organophosphorus compounds. In: Boyer, P.D., Lardy, H. and Myrbäck, K. (Ed.), The Enzymes, 2nd edn, vol. 4, Academic Press, New York, 1960, pp. 541–550.
6.  Reiner, E., Aldridge, W.N. and Hoskin, C.G. (Ed.), Enzymes Hydrolysing Organophosphorus Compounds, Ellis Horwood, Chichester, UK, 1989.
[EC 3.8.2.2 created 1961 as EC 3.8.2.1, transferred 1992 to EC 3.1.8.2, reinstated 2023 as EC 3.8.2.1]
 
 
*EC 4.1.1.87
Accepted name: malonyl-[malonate decarboxylase] decarboxylase
Reaction: a malonyl-[holo malonate decarboxylase acyl-carrier protein] = an acetyl-[holo malonate decarboxylase acyl-carrier protein] + CO2
For diagram of malonate decarboxylase, click here
Other name(s): malonyl-S-ACP decarboxylase; malonyl-S-acyl-carrier protein decarboxylase; MdcD/MdcE; MdcD,E; malonyl-[acyl-carrier-protein] carboxy-lyase
Systematic name: malonyl-[holo malonate decarboxylase acyl-carrier protein] carboxy-lyase
Comments: This enzyme comprises the β and γ subunits of EC 4.1.1.88, biotin-independent malonate decarboxylase but is not present in EC 7.2.4.4, biotin-dependent malonate decarboxylase. It follows on from EC 2.3.1.187, acetyl-S-ACP:malonate ACP transferase, and results in the regeneration of the acetylated form of the acyl-carrier-protein subunit of malonate decarboxylase [5]. The carboxy group is lost with retention of configuration [3].
Links to other databases: BRENDA, EXPASY, KEGG
References:
1.  Schmid, M., Berg, M., Hilbi, H. and Dimroth, P. Malonate decarboxylase of Klebsiella pneumoniae catalyses the turnover of acetyl and malonyl thioester residues on a coenzyme-A-like prosthetic group. Eur. J. Biochem. 237 (1996) 221–228. [DOI] [PMID: 8620876]
2.  Koo, J.H. and Kim, Y.S. Functional evaluation of the genes involved in malonate decarboxylation by Acinetobacter calcoaceticus. Eur. J. Biochem. 266 (1999) 683–690. [DOI] [PMID: 10561613]
3.  Handa, S., Koo, J.H., Kim, Y.S. and Floss, H.G. Stereochemical course of biotin-independent malonate decarboxylase catalysis. Arch. Biochem. Biophys. 370 (1999) 93–96. [DOI] [PMID: 10496981]
4.  Chohnan, S., Akagi, K. and Takamura, Y. Functions of malonate decarboxylase subunits from Pseudomonas putida. Biosci. Biotechnol. Biochem. 67 (2003) 214–217. [DOI] [PMID: 12619701]
5.  Dimroth, P. and Hilbi, H. Enzymic and genetic basis for bacterial growth on malonate. Mol. Microbiol. 25 (1997) 3–10. [DOI] [PMID: 11902724]
[EC 4.1.1.87 created 2008, modified 2023]
 
 
EC 4.1.1.124
Accepted name: malonyl-[acp] decarboxylase
Reaction: malonyl-[acp] = acetyl-[acp] + CO2
Other name(s): decarboxylative ketosynthase; bryQ (gene name); mupG (gene name); pksF (gene name); curC (gene name); jamG (gene name); pedM (gene name)
Systematic name: malonyl-[acyl-carrier protein] carboxy-lyase
Comments: This family of enzymes participates in a process that introduces a methyl branch into nascent polyketide products. The process begins with EC 4.1.1.124, malonyl-[acp] decarboxylase, which converts the common extender unit malonyl-[acp] to acetyl-[acp]. The enzyme is a mutated form of a ketosynthase enzyme, in which a Cys residue in the active site is modified to a Ser residue, leaving the decarboxylase function intact, but nulifying the ability of the enzyme to form a carbon-carbon bond. Next, EC 2.3.3.22, 3-carboxymethyl-3-hydroxy-acyl-[acp] synthase, utilizes the acetyl group to introduce the branch at the β position of 3-oxoacyl intermediates attached to a polyketide synthase, forming a 3-hydroxy-3-carboxymethyl intermediate. This is followed by dehydration catalysed by EC 4.2.1.181, 3-carboxymethyl-3-hydroxy-acyl-[acp] dehydratase (often referred to as an ECH1 domain), leaving a 3-carboxymethyl group and forming a double bond between the α and β carbons. The process concludes with decarboxylation catalysed by EC 4.1.1.125, 4-carboxy-3-alkylbut-2-enoyl-[acp] decarboxylase (often referred to as an ECH2 domain), leaving a methyl branch at the β carbon. The enzymes are usually encoded by a cluster of genes referred to as an "HMGS cassette", based on the similarity of the key enzyme to EC 2.3.3.10, hydroxymethylglutaryl-CoA synthase. cf. EC 4.1.1.87, malonyl-[malonate decarboxylase] decarboxylase.
Links to other databases: BRENDA, EXPASY, KEGG
References:
1.  Simunovic, V. and Muller, R. 3-hydroxy-3-methylglutaryl-CoA-like synthases direct the formation of methyl and ethyl side groups in the biosynthesis of the antibiotic myxovirescin A. Chembiochem 8 (2007) 497–500. [DOI] [PMID: 17330904]
2.  Wu, J., Hothersall, J., Mazzetti, C., O'Connell, Y., Shields, J.A., Rahman, A.S., Cox, R.J., Crosby, J., Simpson, T.J., Thomas, C.M. and Willis, C.L. In vivo mutational analysis of the mupirocin gene cluster reveals labile points in the biosynthetic pathway: the "leaky hosepipe" mechanism. Chembiochem 9 (2008) 1500–1508. [DOI] [PMID: 18465759]
3.  Buchholz, T.J., Rath, C.M., Lopanik, N.B., Gardner, N.P., Hakansson, K. and Sherman, D.H. Polyketide β-branching in bryostatin biosynthesis: identification of surrogate acetyl-ACP donors for BryR, an HMG-ACP synthase. Chem. Biol. 17 (2010) 1092–1100. [DOI] [PMID: 21035732]
[EC 4.1.1.124 created 2023]
 
 
EC 4.1.1.125
Accepted name: 4-carboxy-3-alkylbut-2-enoyl-[acp] decarboxylase
Reaction: a 4-carboxy-3-alkylbut-2-enoyl-[acp] = a 3-alkylbut-2-enoyl-[acp] + CO2
Other name(s): aprG (gene name); corG (gene name); pedI (gene name); mupK (gene name); 3-carboxymethyl-alk-2-enyl-[acyl-carrier protein] decarboxylase
Systematic name: 4-carboxy-3-alkylbut-2-enoyl-[acyl-carrier protein] carboxy-lyase
Comments: This family of enzymes participates in a process that introduces a methyl branch into nascent polyketide products. The process begins with EC 4.1.1.124, malonyl-[acp] decarboxylase, which converts the common extender unit malonyl-[acp] to acetyl-[acp]. The enzyme is a mutated form of a ketosynthase enzyme, in which a Cys residue in the active site is modified to a Ser residue, leaving the decarboxylase function intact, but nulifying the ability of the enzyme to form a carbon-carbon bond. Next, EC 2.3.3.22, 3-carboxymethyl-3-hydroxy-acyl-[acp] synthase, utilizes the acetyl group to introduce the branch at the β position of 3-oxoacyl intermediates attached to a polyketide synthase, forming a 3-hydroxy-3-carboxymethyl intermediate. This is followed by dehydration catalysed by EC 4.2.1.181, 3-carboxymethyl-3-hydroxy-acyl-[acp] dehydratase (often referred to as an ECH1 domain), leaving a 3-carboxymethyl group and forming a double bond between the α and β carbons. The process concludes with decarboxylation catalysed by EC 4.1.1.125, 4-carboxy-3-alkylbut-2-enoyl-[acp] decarboxylase (often referred to as an ECH2 domain), leaving a methyl branch at the β carbon. The enzymes are usually encoded by a cluster of genes referred to as an "HMGS cassette", based on the similarity of the key enzyme to EC 2.3.3.10, hydroxymethylglutaryl-CoA synthase.
Links to other databases: BRENDA, EXPASY, KEGG
References:
1.  Geders, T.W., Gu, L., Mowers, J.C., Liu, H., Gerwick, W.H., Hakansson, K., Sherman, D.H. and Smith, J.L. Crystal structure of the ECH2 catalytic domain of CurF from Lyngbya majuscula. Insights into a decarboxylase involved in polyketide chain β-branching. J. Biol. Chem. 282 (2007) 35954–35963. [DOI] [PMID: 17928301]
2.  Erol, O., Schaberle, T.F., Schmitz, A., Rachid, S., Gurgui, C., El Omari, M., Lohr, F., Kehraus, S., Piel, J., Muller, R. and Konig, G.M. Biosynthesis of the myxobacterial antibiotic corallopyronin A. Chembiochem 11 (2010) 1253–1265. [DOI] [PMID: 20503218]
3.  Grindberg, R.V., Ishoey, T., Brinza, D., Esquenazi, E., Coates, R.C., Liu, W.T., Gerwick, L., Dorrestein, P.C., Pevzner, P., Lasken, R. and Gerwick, W.H. Single cell genome amplification accelerates identification of the apratoxin biosynthetic pathway from a complex microbial assemblage. PLoS One 6:e18565 (2011). [DOI] [PMID: 21533272]
[EC 4.1.1.125 created 2023]
 
 
EC 4.1.1.126
Accepted name: anhydromevalonate phosphate decarboxylase
Reaction: trans-anhydromevalonate 5-phosphate = 3-methylbut-3-en-1-yl phosphate + CO2
Glossary: trans-anhydromevalonate 5-phosphate = (2E)-3-methyl-5-phosphooxypent-2-enoate
3-methylbut-3-en-1-yl phosphate = isopentenyl phosphate
Systematic name: trans-anhydromevalonate 5-phosphate carboxy-lyase
Comments: The enzyme catalyses a step in the archaeal prenyl diphosphate biosynthesis pathway. It requires a prenylated flavin cofactor that is produced by EC 2.5.1.129, flavin prenyltransferase.
Links to other databases: BRENDA, EXPASY, KEGG
References:
1.  Yoshida, R., Yoshimura, T. and Hemmi, H. Reconstruction of the "archaeal" mevalonate pathway from the methanogenic archaeon Methanosarcina mazei in Escherichia coli cells. Appl. Environ. Microbiol. 86:e02889-19 (2020). [DOI] [PMID: 31924615]
[EC 4.1.1.126 created 2023]
 
 
EC 4.2.1.181
Accepted name: 3-carboxymethyl-3-hydroxy-acyl-[acp] dehydratase
Reaction: a 3-carboxymethyl-3-hydroxy-acyl-[acyl-carrier protein] = a 4-carboxy-3-alkylbut-2-enoyl-[acyl-carrier protein] + H2O
Other name(s): aprF (gene name); corF (gene name); curE (gene name); pedL (gene name); 3-carboxymethyl-3-hydroxy-acyl-[acyl-carrier protein] dehydratase
Systematic name: 3-carboxymethyl-3-hydroxy-acyl-[acyl-carrier protein] hydro-lyase
Comments: This family of enzymes participates in a process that introduces a methyl branch into nascent polyketide products. The process begins with EC 4.1.1.124, malonyl-[acp] decarboxylase, which converts the common extender unit malonyl-[acp] to acetyl-[acp]. The enzyme is a mutated form of a ketosynthase enzyme, in which a Cys residue in the active site is modified to a Ser residue, leaving the decarboxylase function intact, but nulifying the ability of the enzyme to form a carbon-carbon bond. Next, EC 2.3.3.22, 3-carboxymethyl-3-hydroxy-acyl-[acp] synthase, utilizes the acetyl group to introduce the branch at the β position of 3-oxoacyl intermediates attached to a polyketide synthase, forming a 3-hydroxy-3-carboxymethyl intermediate. This is followed by dehydration catalysed by EC 4.2.1.181, 3-carboxymethyl-3-hydroxy-acyl-[acp] dehydratase (often referred to as an ECH1 domain), leaving a 3-carboxymethyl group and forming a double bond between the α and β carbons. The process concludes with decarboxylation catalysed by EC 4.1.1.125, 4-carboxy-3-alkylbut-2-enoyl-[acp] decarboxylase (often referred to as an ECH2 domain), leaving a methyl branch at the β carbon. The enzymes are usually encoded by a cluster of genes referred to as an "HMGS cassette", based on the similarity of the key enzyme to EC 2.3.3.10, hydroxymethylglutaryl-CoA synthase. cf. EC 4.2.1.18, methylglutaconyl-CoA hydratase.
Links to other databases: BRENDA, EXPASY, KEGG
References:
1.  Gu, L., Jia, J., Liu, H., Hakansson, K., Gerwick, W.H. and Sherman, D.H. Metabolic coupling of dehydration and decarboxylation in the curacin A pathway: functional identification of a mechanistically diverse enzyme pair. J. Am. Chem. Soc. 128 (2006) 9014–9015. [DOI] [PMID: 16834357]
2.  Gu, L., Wang, B., Kulkarni, A., Geders, T.W., Grindberg, R.V., Gerwick, L., Hakansson, K., Wipf, P., Smith, J.L., Gerwick, W.H. and Sherman, D.H. Metamorphic enzyme assembly in polyketide diversification. Nature 459 (2009) 731–735. [DOI] [PMID: 19494914]
3.  Erol, O., Schaberle, T.F., Schmitz, A., Rachid, S., Gurgui, C., El Omari, M., Lohr, F., Kehraus, S., Piel, J., Muller, R. and Konig, G.M. Biosynthesis of the myxobacterial antibiotic corallopyronin A. Chembiochem 11 (2010) 1253–1265. [DOI] [PMID: 20503218]
4.  Grindberg, R.V., Ishoey, T., Brinza, D., Esquenazi, E., Coates, R.C., Liu, W.T., Gerwick, L., Dorrestein, P.C., Pevzner, P., Lasken, R. and Gerwick, W.H. Single cell genome amplification accelerates identification of the apratoxin biosynthetic pathway from a complex microbial assemblage. PLoS One 6:e18565 (2011). [DOI] [PMID: 21533272]
[EC 4.2.1.181 created 2023]
 
 
EC 4.2.1.182
Accepted name: phosphomevalonate dehydratase
Reaction: (R)-5-phosphomevalonate = trans-anhydromevalonate 5-phosphate + H2O
Glossary: trans-anhydromevalonate 5-phosphate = (2E)-3-methyl-5-phosphooxypent-2-enoate
Systematic name: R-5-phosphomevalonate hydro-lyase
Comments: The enzyme catalyses a step in an archaeal prenyl diphosphate biosynthesis pathway. It belongs to the aconitase X family, and contains a [4Fe-4S] cluster.
Links to other databases: BRENDA, EXPASY, KEGG
References:
1.  Yoshida, R., Yoshimura, T. and Hemmi, H. Reconstruction of the "archaeal" mevalonate pathway from the methanogenic archaeon Methanosarcina mazei in Escherichia coli cells. Appl. Environ. Microbiol. 86:e02889-19 (2020). [DOI] [PMID: 31924615]
2.  Komeyama, M., Kanno, K., Mino, H., Yasuno, Y., Shinada, T., Ito, T. and Hemmi, H. A [4Fe-4S] cluster resides at the active center of phosphomevalonate dehydratase, a key enzyme in the archaeal modified mevalonate pathway. Front Microbiol. 14:1150353 (2023). [DOI] [PMID: 36992929]
[EC 4.2.1.182 created 2023]
 
 
EC 4.2.2.29
Accepted name: peptidoglycan lytic transglycosylase
Reaction: a peptidoglycan chain = a peptidoglycan chain with N-acetyl-1,6-anhydromuramyl-(peptide) at the reducing end + a peptidoglycan chain with N-acetylglucosamine at the non-reducing end
Other name(s): lytic murein transglycosylase; endolytic murein transglycosylase; lytic transglycosylase; endolytic transglycosylase; MtlA; MltB; MltC; MltD; MltE; MltF; MltG; Slt; RlpA; SleB; SpoIID
Systematic name: peptidoglycan N-acetylmuramate—N-acetyl-β-D-glucosamine lyase
Comments: A group of bacterial enzymes that catalyse the non-hydrolytic cleavage of peptidoglycan (PG). The enzymes fragment the polysaccharide chain at the β-1,4-glycosidic bond between N-acetylmuramic acid and N-acetylglucosamine residues by an intramolecular cyclization of the N-acetylmuramyl moiety to yield a 1,6-anhydro-N-acetyl-β-D-muramyl product. Includes endolytic transglycosylase activity that fragments the glycan chain internally and exolytic transgylcosylase activity that cleaves a terminal disaccharide from the end of the glycan strand. The MtlG enzyme of Gram-negative bacteria may function to regulate glycan strand length within the PG polymer.
Links to other databases: BRENDA, EXPASY, KEGG
References:
1.  Holtje, J.V., Mirelman, D., Sharon, N. and Schwarz, U. Novel type of murein transglycosylase in Escherichia coli. J. Bacteriol. 124 (1975) 1067–1076. [DOI] [PMID: 357]
2.  Yunck, R., Cho, H. and Bernhardt, T.G. Identification of MltG as a potential terminase for peptidoglycan polymerization in bacteria. Mol. Microbiol. 99 (2016) 700–718. [DOI] [PMID: 26507882]
3.  Dik, D.A., Marous, D.R., Fisher, J.F. and Mobashery, S. Lytic transglycosylases: concinnity in concision of the bacterial cell wall. Crit. Rev. Biochem. Mol. Biol. 52 (2017) 503–542. [DOI] [PMID: 28644060]
[EC 4.2.2.29 created 2023]
 
 
EC 4.2.3.212
Accepted name: (+)-δ-cadinol synthase
Reaction: (2E,6E)-farnesyl diphosphate + H2O = (+)-δ-cadinol + diphosphate
For diagram of ent-cadinane sesquiterpenoid biosynthesis, click here
Glossary: (+)-δ-cadinol = (1S,4R,4aS,8aR)-1,6-dimethyl-4-(propan-2-yl)-1,2,3,4,4a,7,8,8a-octahydronaphthalen-1-ol = (+)-torreyol
Other name(s): δ-cadinol synthase (ambiguous)
Systematic name: (2E,6E)-farnesyl-diphosphate diphosphate-lyase [(+)-δ-cadinol-forming]
Comments: The enzyme is involved in the biosynthesis of sesquiterpenoids from (2E,6E)-farnesyl diphosphate in fungi such as Boreostereum vibrans and Coniophora puteana.
Links to other databases: BRENDA, EXPASY, KEGG
References:
1.  Zhou, H., Yang, Y.L., Zeng, J., Zhang, L., Ding, Z.H. and Zeng, Y. Identification and characterization of a δ-cadinol synthase potentially involved in the formation of boreovibrins in Boreostereum vibrans of basidiomycota. Nat. Prod. Bioprospect. 6 (2016) 167–171. [DOI] [PMID: 27038475]
2.  Ringel, M., Dimos, N., Himpich, S., Haack, M., Huber, C., Eisenreich, W., Schenk, G., Loll, B. and Bruck, T. Biotechnological potential and initial characterization of two novel sesquiterpene synthases from Basidiomycota Coniophora puteana for heterologous production of δ-cadinol. Microb. Cell Fact. 21:64 (2022). [DOI] [PMID: 35440053]
[EC 4.2.3.212 created 2023]
 
 
EC 4.2.3.213
Accepted name: colleterpenol synthase
Reaction: all-trans-hexaprenyl diphosphate + H2O = colleterpenol + diphosphate
Glossary: colleterpenol = (2S)-2-[(1R,3E,7E,11E)-4,8,12-trimethylcyclotetradeca-3,7,11-trien-1-yl]undeca-5,9-dien-2-ol
Other name(s): CgCS
Systematic name: pentaprenyl-diphosphate diphosphate-lyase [cyclizing, colleterpenol-forming]
Comments: Isolated from Colletotrichum gloeosporioides, a pathogenic fungus that causes bitter rot in variety of crops.
Links to other databases: BRENDA, EXPASY, KEGG
References:
1.  Tao, H., Lauterbach, L., Bian, G., Chen, R., Hou, A., Mori, T., Cheng, S., Hu, B., Lu, L., Mu, X., Li, M., Adachi, N., Kawasaki, M., Moriya, T., Senda, T., Wang, X., Deng, Z., Abe, I., Dickschat, J.S. and Liu, T. Discovery of non-squalene triterpenes. Nature 606 (2022) 414–419. [DOI] [PMID: 35650436]
[EC 4.2.3.213 created 2023]
 
 
EC 4.2.3.214
Accepted name: dolasta-1(15),8-diene synthase
Reaction: geranylgeranyl diphosphate = (5R,12R,14S)-dolasta-1(15),8-diene + diphosphate
For diagram of dolastadiene and δ-araneosene biosynthesis, click here
Glossary: (5R,12R,14S)-dolasta-1(15),8-diene = (3aR,4aS,8aR)-3a,8a-dimethyl-5-methylene-1-(propan-2-yl)-2,3,3a,4,4a,5,6,7,8,8a,9,10-dodecahydrobenzo[f]azulene
Other name(s): Cg113742 (gene name); CgDS
Systematic name: geranylgeranyl-diphosphate diphosphate-lyase [cyclizing, dolasta-1(15),8-diene-forming]
Comments: Isolated from Colletotrichum gloeosporioides, a pathogenic fungus that causes bitter rot in variety of crops.
Links to other databases: BRENDA, EXPASY, KEGG
References:
1.  Bian, G., Rinkel, J., Wang, Z., Lauterbach, L., Hou, A., Yuan, Y., Deng, Z., Liu, T. and Dickschat, J.S. A clade II-D fungal chimeric diterpene synthase from Colletotrichum gloeosporioides produces dolasta-1(15),8-diene. Angew. Chem. Int. Ed. Engl. 57 (2018) 15887–15890. [DOI] [PMID: 30277637]
[EC 4.2.3.214 created 2023]
 
 
EC 4.2.3.215
Accepted name: δ-araneosene synthase
Reaction: geranylgeranyl diphosphate = δ-araneosene + diphosphate
For diagram of dolastadiene and δ-araneosene biosynthesis, click here
Glossary: δ-araneosene = (3aR,5E,9E)-3a,6,10-trimethyl-1-(propan-2-yl)-2,3,3a,4,7,8,11,12-octahydrocyclopenta[11]annulene
Systematic name: geranylgeranyl-diphosphate diphosphate-lyase [cyclizing, δ-araneosene-forming]
Comments: Isolated from the fungus Colletotrichum gloeosporioidea. δ-Araneosene may be involved in the biosynthesis of dolasta-1(15),8-diene (see EC 4.2.3.214, dolasta-1(15),8-diene synthase) and cycloaraneosene (see EC 4.2.3.191, cycloaraneosene synthase).
Links to other databases: BRENDA, EXPASY, KEGG
References:
1.  Bian, G., Rinkel, J., Wang, Z., Lauterbach, L., Hou, A., Yuan, Y., Deng, Z., Liu, T. and Dickschat, J.S. A clade II-D fungal chimeric diterpene synthase from Colletotrichum gloeosporioides produces dolasta-1(15),8-diene. Angew. Chem. Int. Ed. Engl. 57 (2018) 15887–15890. [DOI] [PMID: 30277637]
[EC 4.2.3.215 created 2023]
 
 
EC 4.2.3.216
Accepted name: somaliensene A synthase
Reaction: geranylfarnesyl diphosphate = somaliensene A + diphosphate
For diagram of somaliensene A and B biosynthesis, click here
Glossary: somaliensene A = (1S,5R,6R)-6-methyl-6-[(3E,7E,11E)-trimethyltrideca-3,7,11-trien-1-yl]bicyclo[3.1.1]hept-2-ene
Other name(s): stsC (gene name)
Systematic name: geranylfarnesyl-diphosphate diphosphate-lyase (cyclizing, somaliensene A-forming)
Comments: A sesterterpenoid synthase enzyme isolated from the bacterium Streptomyces somaliensis. The enzyme also produces somalensene B (cf. EC 4.2.3.217, somaliensene B synthase).
Links to other databases: BRENDA, EXPASY, KEGG
References:
1.  Yang, Y., Zhang, Y., Zhang, S., Chen, Q., Ma, K., Bao, L., Tao, Y., Yin, W., Wang, G. and Liu, H. Identification and characterization of a membrane-bound sesterterpene cyclase from Streptomyces somaliensis. J Nat Prod 81 (2018) 1089–1092. [DOI] [PMID: 29553734]
[EC 4.2.3.216 created 2023]
 
 
EC 4.2.3.217
Accepted name: somaliensene B synthase
Reaction: geranylfarnesyl diphosphate = (–)-somaliensene B + diphosphate
For diagram of somaliensene A and B biosynthesis, click here
Glossary: (–)-somaliensene B = (4S)-1-methyl-4-[(5E,9E,13E)-6,10,14-trimethylpentadeca-1,5,9,13-tetraen-2-yl]cyclohex-1-ene
Other name(s): stsC (gene name)
Systematic name: geranylfarnesyl-diphosphate diphosphate-lyase (cyclizing, (–)-somaliensene B-forming)
Comments: A sesterterpenoid synthase enzyme isolated from the bacterium Streptomyces somaliensis. The enzyme also produces somaliensene A (cf. EC 4.2.3.216, somaliensene A synthase).
Links to other databases: BRENDA, EXPASY, KEGG
References:
1.  Yang, Y., Zhang, Y., Zhang, S., Chen, Q., Ma, K., Bao, L., Tao, Y., Yin, W., Wang, G. and Liu, H. Identification and characterization of a membrane-bound sesterterpene cyclase from Streptomyces somaliensis. J Nat Prod 81 (2018) 1089–1092. [DOI] [PMID: 29553734]
[EC 4.2.3.217 created 2023]
 
 
EC 4.2.3.218
Accepted name: variediene synthase
Reaction: geranylgeranyl diphosphate = variediene + diphosphate
For diagram of miscellaneous diterpenoid biosynthesis, click here
Glossary: variediene = (3aR,3bS,6E,10Z,11aR)-3,3,6,10,11a-pentamethyl-2,3,3a,3b,4,5,8,9,11,11a-decahydro-1H-cyclonona[a]pentalene
Other name(s): EvVS
Systematic name: geranylgeranyl-diphosphate diphosphate-lyase (cyclizing, variediene-forming)
Comments: A diterpenoid synthase enzyme isolated from the fungus Aspergillus stellatus.
Links to other databases: BRENDA, EXPASY, KEGG
References:
1.  Qin, B., Matsuda, Y., Mori, T., Okada, M., Quan, Z., Mitsuhashi, T., Wakimoto, T. and Abe, I. An unusual chimeric diterpene synthase from Emericella variecolor and its functional conversion into a sesterterpene synthase by domain swapping. Angew. Chem. Int. Ed. Engl. 55 (2016) 1658–1661. [DOI] [PMID: 26546087]
[EC 4.2.3.218 created 2023]
 
 
EC 4.2.3.219
Accepted name: (2E)-α-cericerene synthase
Reaction: geranylfarnesyl diphosphate = (2E)-α-cericerene + diphosphate
For diagram of sesterterpenoids biosynthesis, click here
Glossary: (2E)-α-cericerene = (1E,4R,7E,11E)-1,7,11-trimethyl-4-[(2E)-6-methylhepta-2,5-dien-2-yl]cyclotetrdeca-1,7,11-triene
Other name(s): EvSS
Systematic name: geranylfarneyl-diphosphate diphosphate-lyase (cyclizing, (2E)-α-cericerene-forming)
Comments: A sesterterpenoid synthase enzyme isolated from the fungus Aspergillus stellatus.
Links to other databases: BRENDA, EXPASY, KEGG
References:
1.  Qin, B., Matsuda, Y., Mori, T., Okada, M., Quan, Z., Mitsuhashi, T., Wakimoto, T. and Abe, I. An unusual chimeric diterpene synthase from Emericella variecolor and its functional conversion into a sesterterpene synthase by domain swapping. Angew. Chem. Int. Ed. Engl. 55 (2016) 1658–1661. [DOI] [PMID: 26546087]
[EC 4.2.3.219 created 2023]
 
 
EC 6.7.1.2
Accepted name: 3-aminoavenalumate diazotase
Reaction: ATP + 3-aminoavenalumate + nitrite = AMP + diphosphate + 3-diazoavenalumate + H2O
Glossary: 3-aminoavenalumate = (2E,4E)-5-(3-amino-4-hydroxyphenyl)penta-2,4-dienoate
3-diazoavenalumate = 1-{3-[(1E,3E)-4-carboxylatobuta-1,3-dien-1-yl]-6-oxocyclohexa-2,4-dien-1-ylidene}diazenium
Other name(s): avaA6 (gene name)
Systematic name: 3-aminoavenalumate:nitrite ligase (AMP-forming)
Comments: The enzyme, characterized from the bacterium Streptomyces sp. RI-77, participates in the biosynthesis of avenalumate, a phenolic acid originally described from oat (Avena sativa). It can also act on 3-aminocoumarate and 3-amino-4-hydroxybenzoate with lower activity.
Links to other databases: BRENDA, EXPASY, KEGG
References:
1.  Kawai, S., Hagihara, R., Shin-Ya, K., Katsuyama, Y. and Ohnishi, Y. Bacterial avenalumic acid biosynthesis includes substitution of an aromatic amino group for hydride by nitrous acid dependent diazotization. Angew. Chem. Int. Ed. Engl. 61 (2022) e202211728. [DOI] [PMID: 36115045]
[EC 6.7.1.2 created 2023]
 
 
*EC 7.1.1.3
Accepted name: ubiquinol oxidase (H+-transporting)
Reaction: 2 quinol + O2[side 2] + 8 H+[side 2] = 2 quinone + 2 H2O[side 2] + 8 H+[side 1]
Other name(s): cyoABCD (gene names); cytochrome bo3 oxidase; cytochrome bb3 oxidase; cytochrome bo oxidase; Cyo oxidase; ubiquinol:O2 oxidoreductase (H+-transporting); ubiquinol:oxygen oxidoreductase (H+-transporting)
Systematic name: quinol:oxygen oxidoreductase (H+-transporting)
Comments: Contains a dinuclear centre comprising heme and copper. This terminal oxidase enzyme generates proton motive force by two mechanisms: (1) transmembrane charge separation resulting from utilizing protons and electrons originating from opposite sides of the membrane to generate water, and (2) active pumping of protons across the membrane. The bioenergetic efficiency (the number of charges driven across the membrane per electron used to reduce oxygen to water) of enzymes that have been characterized so far is 2. cf. EC 7.1.1.7, ubiquinol oxidase ubiquinol oxidase (electrogenic, proton-motive force generating).
Links to other databases: BRENDA, EXPASY, KEGG, PDB
References:
1.  Miyoshi-Akiyama, T., Hayashi, M. and Unemoto, T. Purification and properties of cytochrome bo-type ubiquinol oxidase from a marine bacterium Vibrio alginolyticus. Biochim. Biophys Acta 1141 (1993) 283–287. [DOI] [PMID: 8443214]
2.  de Gier, J.W., Lubben, M., Reijnders, W.N., Tipker, C.A., Slotboom, D.J., van Spanning, R.J., Stouthamer, A.H. and van der Oost, J. The terminal oxidases of Paracoccus denitrificans. Mol. Microbiol. 13 (1994) 183–196. [DOI] [PMID: 7984100]
3.  Howitt, C.A. and Vermaas, W.F. Quinol and cytochrome oxidases in the cyanobacterium Synechocystis sp. PCC 6803. Biochemistry 37 (1998) 17944–17951. [DOI] [PMID: 9922162]
4.  Abramson, J., Riistama, S., Larsson, G., Jasaitis, A., Svensson-Ek, M., Laakkonen, L., Puustinen, A., Iwata, S. and Wikstrom, M. The structure of the ubiquinol oxidase from Escherichia coli and its ubiquinone binding site. Nat. Struct. Biol. 7 (2000) 910–917. [DOI] [PMID: 11017202]
5.  Morales, G., Ugidos, A. and Rojo, F. Inactivation of the Pseudomonas putida cytochrome o ubiquinol oxidase leads to a significant change in the transcriptome and to increased expression of the CIO and cbb3-1 terminal oxidases. Environ. Microbiol. 8 (2006) 1764–1774. [DOI] [PMID: 16958757]
6.  Stenberg, F., von Heijne, G. and Daley, D.O. Assembly of the cytochrome bo3 complex. J. Mol. Biol. 371 (2007) 765–773. [PMID: 17583738]
7.  Yap, L.L., Lin, M.T., Ouyang, H., Samoilova, R.I., Dikanov, S.A. and Gennis, R.B. The quinone-binding sites of the cytochrome bo3 ubiquinol oxidase from Escherichia coli. Biochim. Biophys. Acta 1797 (2010) 1924–1932. [DOI] [PMID: 20416270]
8.  Choi, S.K., Lin, M.T., Ouyang, H. and Gennis, R.B. Searching for the low affinity ubiquinone binding site in cytochrome bo3 from Escherichia coli. Biochim Biophys Acta Bioenerg 1858 (2017) 366–370. [PMID: 28235459]
9.  Choi, S.K., Schurig-Briccio, L., Ding, Z., Hong, S., Sun, C. and Gennis, R.B. Location of the substrate binding site of the cytochrome bo3 ubiquinol oxidase from Escherichia coli. J. Am. Chem. Soc. 139 (2017) 8346–8354. [PMID: 28538096]
10.  Graf, S., Brzezinski, P. and von Ballmoos, C. The proton pumping bo oxidase from Vitreoscilla. Sci. Rep. 9:4766 (2019). [DOI] [PMID: 30886219]
[EC 7.1.1.3 created 2011 as EC 1.10.3.10, modified 2014, transferred 2018 to EC 7.1.1.3, modified 2023]
 
 


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